Atosiban may confer therapeutic benefits to specific subpopulations in assisted reproductive technology. The Phase I Atosiban study indicated potential improvements in live birth rates among women with previous implantation failure undergoing frozen-thawed blastocyst transfer who exhibited abnormal uterine contractions, although these findings did not reach statistical significance. Therefore, further investigations are warranted to thoroughly elucidate the efficacy of atosiban and to evaluate whether uterine contractions can serve as a reliable biomarker for its targeted application.

This is a single-centre, randomised, triple-blind, placebo-controlled trial aiming to enrol 792 infertile women aged 20–40 years with a history of at least one previous embryo implantation failure and abnormal uterine contractions prior to single blastocyst-stage embryo transfer. Eligible participants will be randomly assigned in a 1:1 ratio to receive either intravenous atosiban or a placebo before embryo transfer. The primary outcome is live birth rate, with secondary outcomes encompassing various pregnancy and perinatal parameters. Randomisation will be stratified by age and transfer type. Intention-to-treat analysis will be performed using generalised linear models. The trial will be monitored by an independent data and safety monitoring committee, including one interim analysis.

This study has been approved by the Institutional Ethics Committee of Northwest Women’s and Children’s Hospital (No. 2025-058-02). Written informed consent will be obtained from all participants. The study results will be disseminated at scientific conferences and published in peer-reviewed journals.

NCT07185230.

Prolonged weaning from invasive mechanical ventilation is a major challenge in critically ill patients failing a spontaneous breathing trial. Levosimendan, a calcium sensitiser, has been shown to improve respiratory muscle function. However, its effect on clinically relevant endpoints in difficult to wean patients has not yet been investigated. We aim to assess whether levosimendan shortens the weaning process in invasively ventilated intensive care unit (ICU) patients who fail a separation attempt. The objective is to assess the effect of levosimendan on the number of ventilator-free days and alive at day 28.

The WEANing with LEvoSimendan Study (WEANLESS) is an investigator-initiated, multicentre, double-blind, parallel-group, randomised clinical superiority trial. Adult invasively ventilated patients who failed a separation attempt are randomly assigned to receive either intravenous levosimendan (intervention) or placebo (control). The primary outcome is the number of ventilator-free days and alive at day 28 from randomisation. WEANLESS also evaluates the effects of levosimendan on patient-reported outcomes, measured through daily dyspnoea scores and uses an EQ-5D-5L questionnaire. Additionally, we will evaluate healthcare resource utilisation and intensive care capacity, assessed through reintubation rates, ICU readmissions within 90 days, the need for non-invasive respiratory support and ICU length of stay. WEANLESS includes a pharmacokinetic analysis of levosimendan and its metabolites.

WEANLESS is the first clinical study that is sufficiently powered to determine the effect of intravenous levosimendan in difficult to wean patients on the duration of weaning from invasive ventilation.

WEANLESS is registered before the inclusion of the first patient at clinicaltrials.gov; the study protocol has been approved by the relevant ethics committee. Its findings will be disseminated through presentations at scientific conferences and publications in a peer-reviewed journal.

NCT07105202.

Sedation is commonly used in critically ill patients to facilitate procedures and care as well as provide comfort but can carry risks such as delirium and prolonged mechanical ventilation. Although current guidelines advocate for light sedation, sedation practices are influenced by clinicians’ subjective interpretations. Patients and families may experience distress and unmet needs, and little is known about their perspectives and experiences in the context of contemporary light sedation practices.

This study aimed to understand the perceptions and experiences of both patient and family members in the intensive care unit (ICU) of current sedation practices.

Canadian, closed, mixed ICU setting.

Critically ill adult patients and adult family members.

Patients and family members were interviewed, using a semi-structured interview questionnaire, and Braun and Clarke inductive thematic analysis was used to identify themes and subthemes in the data.

We conducted semi-structured interviews with 10 family members and 10 patients. Family members and patients reported that sedation was needed for patient comfort. Family members also described the need for sedation for patient and staff safety, as well as their own comfort. While both groups described sedation as necessary for enduring the medical procedures in the ICU, both groups reported concerns of sedation use, including negative physiological and cognitive patient outcomes. Patients and family members also recommended strategies for improving how sedation use is communicated in the ICU.

Perceptions and experiences of patient and families with sedation care practices in the ICU were multifaceted with both positive and negative outcomes reported including psychological and emotional concerns with sedation use. Key recommendations were provided for improving sedation practices with families emphasising the need for family-centred care and patients highlighting the need for self-determination.

Tinnitus is the perception of sound without an external source, often considered a phantom percept similar to phantom limb sensations, resulting from maladaptive plasticity in the brain. The condition lacks an established biomarker for diagnosis but recent studies have linked it to neural changes. The Tinnitus Detection consortium aims to identify and validate potential biomarkers for tinnitus presence and intensity.

This multicentre prospective case–control study will recruit 560 adults (280 chronic tinnitus; 280 controls). Participants will complete standardised audiological and questionnaire assessments and then undergo 64-channel electroencephalography (and magnetoencephalography at one site) to record event-related potentials during (1) a cortical gap prepulse inhibition of the acoustic startle (GPIAS) paradigm assessing gap-related inhibition of the N1 response and (2) an omission auditory oddball paradigm quantifying mismatch negativity and P300 as candidate biomarkers of tinnitus presence and loudness.

The identification of a biomarker for tinnitus is crucial for developing personalised diagnosis and treatment: There is a need for updated guidelines and more effective tinnitus treatments, as existing interventions often rely on subjective measures. The success of biomarkers like GPIAS and oddball paradigms could significantly improve the reliability of tinnitus diagnosis and treatment, marking a transformative step in the field.

NCT06520865.

As fatigue is among the most frequent manifestations of post-COVID syndrome (PCS), this study aimed to assess the prevalence and severity of cognitive and physical fatigue after occupational SARS-CoV-2 infection and to identify sociodemographic, clinical and occupational predictors of fatigue severity.

Cross-sectional analysis of a multicentre prospective registry.

Six German Social Accident Insurance hospitals distributed across Germany, providing standardised post-COVID assessments for individuals with persistent symptoms following occupational SARS-CoV-2 infection.

Workers with confirmed SARS-CoV-2 infection recognised as an occupational disease or work-related accident who presented with persistent symptoms and were enrolled in a multicentre post-COVID registry.

Cognitive and physical fatigue severity assessed using validated self-administered questionnaires (Fatigue Scale for Motor and Cognitive Functions, Modified Fatigue Impact Scale and Würzburg Fatigue Inventory for Multiple Sclerosis). Clinical relevance was determined based on established cut-offs reported in the literature. Fatigue severity was operationalised using median splits of the respective subscales to identify factors associated with higher fatigue levels.

Among 1511 registry cases, 628 participants had complete fatigue data. Median age was 54 years, 77% were female and most worked in nursing (43%) or educational/care professions (19%). Clinically relevant fatigue was highly prevalent: cognitive fatigue affected 78%–93% and physical fatigue 87%–98%. Both fatigue dimensions were positively correlated with older age, work incapacity and persistent symptom burden. In multivariate analyses, a higher number of acute symptoms was associated with lower odds of cognitive fatigue (adjusted OR 0.39, 95% CI 0.19 to 0.81), while physical fatigue remained associated with profession (adjusted OR 2.04, 95% CI 1.17 to 3.59). Sex, pre-existing conditions, hospitalisation and variant wave were not significant predictors in either model.

Fatigue is a prevalent and disabling PCS-symptom among occupationally exposed workers. Distinct determinants of cognitive and physical fatigue emphasise the need for early recognition, targeted management and rehabilitation strategies to support recovery and work reintegration.

Chronic musculoskeletal pain is an occupational health concern among surgeons, with spinal pain being commonly reported. Exercise-based physiotherapy is recommended for reducing chronic spinal pain; however, the treatment effects are modest and may vary across clinical subgroups. Mechanical Diagnosis and Therapy (MDT) is a classification-based approach that uses a standardised clinical examination to guide exercise-based interventions and self-management strategies, and may offer advantages over non-direction-specific generalised exercise in selected patients.

This pragmatic, two-arm, parallel-group randomised controlled superiority trial will compare MDT with generalised exercise in surgeons with chronic spinal pain and a confirmed directional preference, with a planned recruitment of 62 participants (31 per group). Participants will be randomised 1:1 using a computer-generated allocation sequence in Research Electronic Data Capture (REDCap), with stratification by sex and permuted blocks of undisclosed size. Interventions will be delivered in routine physiotherapy practice with flexible scheduling within predefined boundaries (maximum six supervised sessions; most expected within the first 12 weeks), with a follow-up period of 26 weeks.

The primary outcome is the between-group difference in average pain intensity over the preceding 7 days at 12 weeks, measured using the Numeric Pain Rating Scale and adjusted for baseline pain intensity.

The secondary and exploratory outcomes include functional limitations, health-related quality of life, fear of movement, pain catastrophising, pain self-efficacy, therapeutic alliance, exercise adherence and patient global impression of change, assessed at baseline and at 4, 12 and 26 weeks (where applicable). Treatment effects will be analysed using linear mixed-effects models under the intention-to-treat principle.

Ethical approval has been obtained from the North Denmark Region Committee on Health Research Ethics (N-20240046). The findings will be disseminated through peer-reviewed publications and conference presentations.

NCT07293130.

Potentially inappropriate prescriptions (PIPs) in older adults, such as long-term use of benzodiazepines, proton pump inhibitors without indication or antipsychotics in dementia, are associated with adverse events and increased healthcare utilisation. Despite clinical guidelines discouraging their use, PIPs remain frequent in primary care. An audit and feedback (A&F) intervention of PIPs to general practitioners (GPs), led by pharmacists, may reduce the prescription of PIPs in primary care.

A two-arm, pragmatic, controlled trial will be conducted to evaluate the effectiveness of an A&F-based intervention and a pharmacist-led intervention to reduce the proportion of patients aged ≥65 years receiving inappropriate prescriptions. A total of 170 participating GPs, 85 per group, are required. GPs will be randomised into intervention or control groups (1:1). The intervention includes feedback reports, pharmacist-led academic detailing and access to online training modules. The primary outcome is the proportion of older adults receiving at least one PIP at 12 months as well as the total number of PIPs. A random effects Tobit regression model, censored at 0 and 100, will be used to estimate between-group differences adjusted for baseline prescribing. Subgroup analyses will explore heterogeneity of effect by baseline prescribing level and healthcare region. Implementation outcomes, including reach, fidelity, engagement and maintenance, will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework, combining quantitative and qualitative data.

Ethical approval was obtained by the Balearic Island Committee Ethics (IB5219/23PI). Study findings, including primary and secondary outcomes and qualitative implementation results, will be disseminated through peer-reviewed publications and stakeholder reports.

ISRCTN14449434.

Non-muscle-invasive bladder cancer is often treated with repeated weekly intravesical instillations of chemotherapy or immunotherapy. The number of instillations received influences the risk of recurrence and progression; thus, treatment completion is crucial. However, previous research indicates that nearly half of patients do not adhere to treatment for various reasons. This scoping review aims to define the concept of treatment adherence to intravesical instillation therapies and identify and map the factors that influence treatment adherence in intravesical instillation therapies.

This scoping review will adhere to the Joanna Briggs Institute’s Manual for Evidence Synthesis and will be reported in accordance with the PRISMA Extension for Scoping Reviews. A comprehensive search strategy will be employed to guide the literature search across databases, including MEDLINE, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Central Register of Controlled Trials.

We will include studies on intravesical instillation therapies with BCG or Mitomycin C for non-muscle-invasive bladder cancer, as well as studies that describe factors influencing patients’ adherence to treatment. Screening of abstracts and full texts, as well as data charting, will be performed independently by two researchers using the Covidence software. We will collect and chart data concerning characteristics of the source and setting, treatment specifics, reasons for non-adherence and any factors that affect adherence.

We will summarise each included source and present the identified factors in a narrative synthesis. Furthermore, we will describe how the results inform the review objective.

Ethical approval is not required for this scoping review, as all data have been published. The findings of the scoping review will be disseminated in a scientific publication and widely presented to researchers, healthcare professionals and patients.

Arginine vasopressin (AVP) and oxytocin (OXT) are both hormones released from the posterior pituitary. While AVP primarily regulates water reabsorption in the kidneys, OXT plays a key role in socioemotional functioning. Due to the anatomical proximity, disruptions of the AVP system leading to AVP deficiency (AVP-D) may also affect the OXT system, possibly resulting in an additional OXT deficiency. This hypothesis was recently proven by using the 3,4-methylenedioxymethamphetamine stimulation tests and identifying OXT deficiency in patients with AVP-D, linked to increased anxiety and impaired emotion recognition. Despite these findings, OXT replacement therapy is not currently established as a treatment for AVP-D and long-term replacement therapy remains unexplored.

This is a randomised, double-blind, placebo-controlled, parallel-group trial enrolling adults with AVP-D. Participants are randomised 1:1 to receive intranasal OXT (Syntocinon, 24 IU twice daily) or placebo for 28 days. The primary endpoint is a composite binary outcome defined as a clinically meaningful improvement in either trait anxiety (≥5-point reduction in State-Trait Anxiety Inventory-Trait Score) or emotion recognition (≥4-point increase in EmBody/EmFace task performance). Secondary outcomes include empathy, stress reactivity, neuroimaging markers of amygdala activity, additional psychological measures, metabolic parameters and safety outcomes, including hyponatraemia. Analyses will follow the intention-to-treat principle, with Fisher’s exact test used for the primary outcome and mixed-effects models for secondary endpoints.

The study has been approved by the competent ethics committees and regulatory authorities in Switzerland and the European Union. The following institutions granted ethical approval: Ethikkommission Nordwest- und Zentralschweiz (EKNZ), project number EKNZ 2023–01010 and the Erasmus MC MERC, EU-CT number 2024–5 16 813-19-00. Results will be published in open-access, peer-reviewed journals and disseminated via scientific meetings, media communication and lay summaries provided to participants. De-identified individual participant data will be made available on reasonable request following publication.

NCT06036004.

Leprosy is a chronic disease caused by the bacillus Mycobacterium leprae and remains a public health concern in endemic countries. Early diagnosis is fundamental to prevent transmission and irreversible disabilities. Histopathological identification of acid-fast bacilli in tissue specimens is traditionally considered the laboratory reference standard; however, its sensitivity is limited, particularly in paucibacillary forms. Immunohistochemistry (IHC) has been proposed as an adjunctive diagnostic tool for detecting M. leprae antigens in tissue samples, but its diagnostic accuracy has not been systematically synthesised. This protocol outlines a systematic review aimed at evaluating the sensitivity and specificity of IHC in the laboratory diagnosis of leprosy.

This systematic review of diagnostic test accuracy studies will include analytical observational studies and clinical trials evaluating IHC in human subjects with suspected leprosy. The reference standard will be defined as the identification of acid-fast bacilli in skin biopsy specimens from patients with compatible clinical presentation using conventional staining methods (eg, Fite-Faraco), with the exclusion of alternative mycobacterial infections when applicable. Searches will be conducted in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, Scopus, Web of Science and BVS/LILACS (Biblioteca Virtual em Saúde/Latin American and Caribbean Health Sciences Literature), as well as grey literature sources, at 31 May 2026. Two independent reviewers will perform study selection, data extraction using a standardised Microsoft Excel form and risk of bias assessment using the Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity estimates will be calculated. If appropriate, a bivariate random-effects meta-analysis will be conducted using RevMan (Review Manager) and Stata.

Ethical approval is not required because this study will use publicly available data. The results will be submitted to a peer-reviewed journal and presented at scientific conferences.

Patient and public involvement (PPI) in research is increasingly recognised for its potential to enhance feasibility, improve relevance and foster collaboration at different stages of a study. Reporting guidelines such as GRIPP2 (Guidance for Reporting Involvement of Patients and the Public) have been developed to help improve completeness and transparency in PPI reporting. This meta-research project aims to assess the impact of the GRIPP2 reporting guidelines through citation and alternative metrics, analysing its uptake or adoption across authors, institutions, journals and countries, as well as its practical application in reporting PPI within diverse research designs.

This protocol for a meta-research project consists of two studies. In Study 1, we will conduct a search across Web of Science, Scopus and Google Scholar to identify all publications citing the GRIPP2 guidelines (planned for July 2026 using forward citation analysis). Retrieved records will undergo standardised processing and structured de-duplication to ensure each citing article is represented once. Following de-duplication, data from unique citations—including title, publication year, journal, subject category, keywords, document type, citations, authors’ names, institutional affiliations, country and funding sources—will be collected. Citation counts, alternative metrics (eg, mentions in policy documents, news media) and knowledge production patterns across authors, institutions, journals and countries will be analysed to assess GRIPP2’s impact and uptake of the guidelines. Descriptive analyses will be conducted (including the number of papers, citations, authors, countries, journals, keywords, funding, field distribution and main collaboration metrics). Network analyses will be carried out to study the structure of collaborations. In Study 2, we will evaluate a random sample of 300 research articles citing GRIPP2, including randomised trials (n=100), systematic reviews with meta-analyses (n=100) and health economic evaluations (n=100). If an insufficient number of citing studies are available within these categories, we will include additional study types identified in Study 1 (eg, study protocols, observational studies, mixed-methods or qualitative research studies and other types of reviews). Reporting and PPI practices in each article will be extracted by at least two researchers using a standardised data extraction form. Information on general, methodological and PPI items will be analysed and reported, stratified by study design (eg, randomised trials vs systematic reviews vs health economic evaluations).

Due to the nature of the proposed study, no ethical approval will be required. All data will be deposited in a cross-disciplinary public repository. It is anticipated the study findings could be relevant to a variety of audiences. Study findings will be disseminated at scientific conferences and published in peer-reviewed journals.

Open Science Framework: https://osf.io/et85d

Postoperative delirium (POD) is a common complication following cardiac surgery and is closely associated with adverse clinical outcomes. The effect of perioperative dexmedetomidine on reducing POD remains controversial in the existing literature. In our previous meta-analysis, we obtained preliminary evidence suggesting that dexmedetomidine may reduce the incidence of POD by improving sleep quality, which may partly explain the heterogeneity reported in previous studies. Based on these findings, the present randomised controlled trial aims to test the hypothesis that preoperative intranasal administration of dexmedetomidine reduces the incidence of POD in patients undergoing cardiopulmonary bypass assisted cardiac surgery by enhancing preoperative sleep quality.

This trial is a single-centre, investigator-initiated, parallel, double-blind, randomised, placebo-controlled trial. Individuals aged 18 years or older who are scheduled for elective cardiopulmonary bypass—assisted cardiac surgery will be enrolled in the study. The planned sample size is 686. Participants will be randomly assigned to either the dexmedetomidine group receiving two doses of dexmedetomidine (1.5 µg/kg according to ideal body weight) administered between 21:00 and 21:30 on the night before surgery and 15 min before anaesthesia induction, or the placebo group, receiving an equivalent volume of normal saline at the same time points. The primary outcome is the incidence of delirium within 7 days after surgery. Secondary outcomes include the severity, subtypes and duration of delirium, length of postoperative hospital stay, in-hospital all-cause mortality, postoperative sleep assessed by the Numerical Rating Scale score, pain intensity, postoperative anxiety and depression scores. Mediation analyses will be conducted using the preoperative Sleep Quality Index to assess whether dexmedetomidine reduces POD by improving preoperative sleep quality. The Baron and Kenny causal steps framework in conjunction with bootstrap resampling will be employed to estimate the direct, indirect and total effects.

The study is approved by the Institutional Review Board of Xijing Hospital (KY20242259). Written informed consent will be obtained from all participants. The results will be submitted for publication in peer-reviewed journals.

NCT06619912.